Expert opinion on medical diagnostics最新文献

Introduction: People with hyperkinetic movements have always attracted the attention of the public and professionals. Alert colleagues noticed families in which a disease passed from generation to generation around Lake Maracaibo in Venezuela. This study led in 1993 to the localization of the gene for Huntington disease on chromosome 4. The genetic basis of many other familial and sporadic diseases has been identified on human DNA.

Areas covered: The clinical presentation of hyperkinesias remains the starting point for diagnosis, but differential diagnosis is a long, difficult process, the first step being to differentiate between inherited and non-inherited forms. The need to know the diagnosis is of major importance for patient and family. Knowledge about the cause limits the number of extra diagnostics. This review of the literature presents the most frequently occurring genetically-determined forms of hyperkinesias, mainly chorea and dystonia and tries to give some practical guidelines.

Expert opinion: The final part of the review will offer some thoughts and views for future development in a world which probably has more knowledge than we can handle. The drive to find a diagnosis is rewarded by the patient but one also needs to reflect on the use of medical care.

Huntington's disease (HD) is a devastating autosomal-dominant neurodegenerative condition caused by a CAG repeat expansion in the gene encoding huntingtin which is characterised by progressive motor impairment, cognitive decline and neuropsychiatric disturbances. There are currently no disease-modifying treatments available to patients, but a number of therapeutic strategies are currently being investigated, chief among them are nucleotide-based 'gene silencing' approaches, modulation of huntingtin post-translation modification and enhancing clearance of the mutant protein. In 2008, the authors' review highlighted the need to develop and validate biomarkers and provided a systematic head-to-head comparison of such measures. They searched the PubMed database for publications, which covered each of the subheadings mentioned below. They identified from these list studies which had relevance to biomarker development, as defined in their previous review. Building on a tradition of collaborative research in HD, great advances have been made in the field since that time and a range of outcome measures are now being recommended in order to assess efficacy in future therapeutic trials.

Introduction: Despite the availability of a safe and effective vaccine, chronic hepatitis B virus (HBV) infection continues to be a global health concern with an estimated 350 - 400 million people infected worldwide. Globally, HBV is the leading cause of chronic liver disease that may progress to cirrhosis and hepatocellular carcinoma. Therefore, accurate diagnosis and classification of the disease are important to determine whether therapy is needed.

Areas covered: The review contains an overview of recent data on the existing and emerging developments in the molecular diagnostic and monitoring tools for chronic liver disease.

Expert opinion: Monitoring of HBV viral load is the most widely used method in assessing liver disease severity, predicting development of cirrhosis and hepatocellular carcinoma, deciding initiation of antiviral therapy, assessing treatment response as well as early detection of emergence of drug resistance. Some recent studies have downplayed the importance of viral load in HBV management. Phenotyping/genotyping methods can establish emergent resistance to antivirals. Increasing number of reports suggest that clinical outcome and efficacy of antiviral treatment might vary with HBV genotype and precore/core promoter mutants. The importance of covalently closed circular DNA is also becoming apparent in this regard. Further studies on the development of newer molecular methods for a better management of chronic hepatitis B (CHB) will minimize morbidity in CHB.

Introduction: The imaging needs in the individual neuroendocrine tumor (NET) patient are very diverse and the choice of method, or combination of techniques, depends on the characteristics of the particular type of NET and its presentation.

Areas covered: The various morphological and functional imaging methods and important methodological aspects are described. The imaging requirements for the various NET subtypes are explained and typical NET image findings are described and illustrated.

Expert opinion: The choice of the optimum imaging techniques is not only a matter of sensitivity and specificity but must also be considered in the light of the local availability and expertise in the department. Familiarity with contrast-enhancement technique for computed tomography (CT) and magnetic resonance imaging (MRI) is important in the interpretation and understanding of the imaging results. MRI including diffusion weighted imaging (DWI) for oncological imaging has been reported to improve tumor visualization and reader confidence and is expected to similarly be beneficial for NET imaging. Positron emission tomography (PET) using 68Ga-labeled somatostatin analogs is in several aspects superior to somatostatin receptor scintigraphy using Octreoscan®. Molecular imaging problem-solving tools, when PET/CT using 68Ga-labeled somatostatin analogs fails, are PET/CT with 11C-5-HTP and 18F-DOPA.

Introduction: High-resolution ultrasound (US) of the peripheral nerves is now a standard means of assessing neuromuscular disorders in many centers. Currently used in conjunction with electrodiagnostic (EDX) studies, nerve US is especially effective in the diagnosis of entrapment neuropathies.

Areas covered: This article reviews the basic physics of peripheral nerve US, guidelines for its current use and future directions. Advantages of using nerve US alongside EDX studies are outlined along with current limitations of testing. The role of US in the diagnosis of entrapment neuropathy is emphasized, particularly in carpal tunnel syndrome (CTS). US assisted diagnosis of peripheral nerve tumors, hereditary neuropathy and dysimmune neuropathy and traumatic injuries is also described.

Expert opinion: US is a powerful tool in the assessment of peripheral nerve disease. Nerve US is an evolving, young discipline. There is still much to learn, but current evidence supports US imaging of all patients presenting for evaluation of possible mononeuropathy. With improvements in resolution, the introduction of US contrast agents and objective measures of nerve echogenicity, there is promise for further expanding its role in the diagnosis of all peripheral neuropathies.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease and nowadays it is recognized as one of main leading cause of liver fibrosis worldwide. Because of the high risk to develop cirrhosis and hepatocellular carcinoma, the early assessment of liver fibrosis is an important part of the management of NAFLD patients. To date, histological evaluation of liver biopsy represents the cornerstone for staging and grading liver fibrosis. However, due to the several drawbacks of this approach, during the last decade clinicians and researchers are dedicating their efforts to the identification of novel, safe and effective non-invasive tools to assess liver fibrosis. As due to their accuracy degree, transient elastography (TE) and serum biomarkers seem to be able to replace liver biopsy to determine at least the presence of significant liver fibrosis. The combination of these tools may greatly enhance their diagnostic power. Nevertheless, investigations of new imaging techniques and the molecular pathogenesis of NAFLD are necessary to develop reliable non-invasive alternative approaches to liver biopsy. Here, the authors discuss the salient aspects of diagnostic performance of TE and serum biomarkers available for detecting hepatic fibrosis in NAFLD and provide suggestions as to how these non-invasive techniques can be incorporated into diagnostic management of patients affected by this disease.

Introduction: Fungal keratitis is prevalent in tropical regions of the world and is being increasingly recognized as an important cause of ocular morbidity. Early diagnosis and appropriate treatment are essential to avoid blindness. Clinical impression is often suggestive but clinical features may vary considerably and no one clinical feature may be pathognomonic of fungal infection.

Areas covered: This review describes a combination of methods for the diagnosis of fungal keratitis. Both in vivo and in vitro techniques are described along with their advantages and limitations. In vivo confocal microscopy has made it easier for ophthalmologists to back up their clinical suspicion. In vitro methods include microscopy and culture for fungi. A wide range of conventional and molecular techniques are currently available that provide rapid diagnosis of fungal keratitis.

Expert opinion: Owing to the sensitivity and specificity of over 80%, when available, confocal microscopy could be useful for the diagnosis of fungal keratitis in the clinic. Among the laboratory techniques, a 10% potassium hydroxide wet mount or Gram stain are simple and sensitive enough to be adopted as office methods by ophthalmologists to rule out fungal etiology in patients with microbial keratitis. Empiric antifungal therapy is discouraged and confirmation of the diagnosis prior to institution of treatment is recommended.

Introduction: Standardized methods for accurate tumor classification are of critical importance for cancer diagnosis and treatment, particularly in diagnostically-challenging cases where site-directed therapies are an option. Molecular diagnostics for tumor classification, subclassification and site of origin determination based on advances in gene expression profiling have translated into clinical practice as complementary approaches to clinicopathological evaluations.

Areas covered: In this review, the foundational science of gene expression-based cancer classification, technical and clinical considerations for clinical translation, and an overview of molecular signatures of tumor classification that are available for clinical use will be discussed. Proposed approaches will also be described for further integration of molecular tests for cancer classification into the diagnostic paradigm using a tissue-based strategy as a key component to direct evaluation.

Expert opinion: Increasing evidence of improved patient outcomes with the application of site and molecularly-targeted cancer therapy through use of molecular tools highlights the growing potential for these gene expression-based diagnostics to positively impact patient management. Looking forward, the availability of adequate tissue will be a significant issue and limiting factor as cancer diagnosis progresses; when the tumor specimen is limited, use of molecular classification may be a reasonable early step in the evaluation, particularly if the tumor is poorly-differentiated and has atypical features.

Introduction: Current diagnostic methods for ovarian cancer have limited performance. Recent advances within the field of epigenetics have shifted the clinical implementation of epigenetic biomarkers as a diagnostic approach from a dream for the future to a present-day consideration. Patients could potentially benefit greatly from this novel diagnostic approach.

Areas covered: Epigenetic mechanisms in cancer are discussed, with a focus on potential diagnostic epigenetic biomarkers in ovarian cancer in tissue and body fluids. A literature search was undertaken (on 22-09-2011) for these subjects using the search syntax ((((((((((((((("ovarian") OR "ovary") OR "ovarian cancer") OR "ovarian cancers") OR "cancer of the ovary") OR "tumour of the ovary") OR "ovarian tumor") OR "ovarian tumors") OR "ovarian tumour") OR "ovarian tumours") OR "ovarian neoplasm") OR "ovarian neoplasms" OR "ovarian carcinoma") OR "ovarian carcinomas") OR "carcinoma of the ovary")) AND ((((((((("epigenetics") OR "epigenetic") OR "epigenome") OR "methylation") OR "hypermethylation") OR "chromatin modification") OR "histone") OR "histones") OR "acetylation")

Expert opinion: To date no single epigenetic biomarker is able to accurately detect early ovarian cancer in either tissue or body fluids. A panel of epigenetic biomarkers based on aberrant DNA methylation in body fluids, especially blood, has the best chance of being implemented in clinical practice, as it is semi-invasive. However, progression toward clinical use is hampered by the lack of detection techniques combining high throughput and accuracy with low cost, by difficulties in establishing reliable reference values and by the heterogeneous nature of ovarian cancer. Until addressed, implementation as a diagnostic measure complimenting current techniques in select cases seems a far way to go, and implementation as a primary screening tool is yet even farther away.

Introduction: The past decade has seen an explosion of functional magnetic resonance imaging (MRI) studies in neuroscience. As the technology progresses, it is now possible to carry out longitudinal studies using functional MRI. Such studies can be used to understand the progression of mental and neurological disorders and the effectiveness of different treatments by obtaining direct measures of brain activity as well as markers of tissue health and connectivity.

Areas covered: We review six popular neuroimaging tools that can be used for longitudinal studies: blood oxygen level-dependent (BOLD)-weighted imaging, BOLD-based functional connectivity, arterial spin labeling, dynamic R2* imaging, voxel-based morphometry, and diffusion tensor imaging.

Expert opinion: Each of these techniques is targeted to probe a specific feature of brain function or brain structure and can reveal important information about the progression of a pathological condition. We anticipate that in the near future, the MRI techniques discussed here may become standard tools in clinical use and will not be used for research purposes only.